Ozone is the principal oxidant air pollutant in most American cities. Our program has established that the pathobiologic response of the mammalian respiratory system to inhalation of ambient concentrations of ozone focuses on the epithelium and varies by species, position within the airway tree and duration of exposure. The focus of this renewal will be the cellular, physiologic, and molecular mechanisms by which exposure to oxidant air pollutants, in concert with allergens, contributes to the development of asthma. The overall hypothesis being tested is that the episodic nature of environmental exposure to oxidant air pollutants: a) promotes the development of asthma and exacerbates the allergen response in asthmatics by altering the homeostasis of the airway epithelial-mesenchymal trophic unit in adults; and b) elevates the severity of asthma in the young by fundamentally altering the postnatal development of these trophic interactions. These changes result from continual cycles of acute injury, inflammation and repair superimposed on the immune response to allergen exposure. Project 2 will address the impact of the immune response and inflammation on the organization of the epithelial-mesenchymal trophic unit through three specific aims by determining alterations in factors which contribute to development of asthma in neonatal and adult monkeys exposed to ozone.: 1) augmentation of allergic sensitization; 2) augmentation of recruitment and proliferation of leukocytes; 3) cytokine-induced expression of mucin genes. All three projects will compare responses in the same neonatal and adult rhesus monkeys following episodic exposures to ozone and repeated challenge with a human allergen, house dust mite, during either the injury/inflammation phase of ozone exposure or the repair phase.